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. 2016 Dec;4(1):20.
doi: 10.1186/s40635-016-0093-2. Epub 2016 Jul 7.

The Effect of Plasma From Septic ICU Patients on Healthy Rat Muscle Mitochondria

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Free PMC article

The Effect of Plasma From Septic ICU Patients on Healthy Rat Muscle Mitochondria

Jonathan Grip et al. Intensive Care Med Exp. .
Free PMC article

Abstract

Background: Although sepsis-induced organ failure is a major cause of death in ICU worldwide, the associated mitochondrial dysfunction is not fully characterized and there is presently no evidence of causality. In this study, we examined whether a central factor in septic plasma could directly affect respiratory function of healthy rat muscle mitochondria.

Methods: ICU patients with severe sepsis or septic shock were recruited within 24 h of admission together with age-matched controls. Blood samples were centrifuged and immediately frozen. Two trials were performed, and mitochondrial respiration was analyzed using an Oxygraph chamber with a Clark-electrode. (1) Isolated mitochondria from the rat skeletal muscle were divided and incubated for 30 min with plasma from patients or postoperative controls (n = 10). Respiration was normalized for citrate synthase activity. (2) Permeabilized muscle fibers from rats were divided and incubated with plasma from patients or healthy controls, for 30 and 120 min, and analyzed for mitochondrial respiration (n = 10). Respiration was normalized for wet weight. Primary outcome was state 3 respiration, corresponding to the maximal respiration initiated by ADP and energy substrates (malate and pyruvate). T test was used for statistical comparison.

Results: No differences in respiratory function of the mitochondria were seen between the groups in either of the experiments. (1) State 3 respiration of isolated mitochondria were 19.9 ± 6.7 vs. 20.2 ± 8.8 nmol O2 × U CS(-1) × min(-1) for sepsis vs. control, respectively. (2) State 3 respiration for fibers incubated with septic and control plasma were after 30 min 2.6 ± 0.3 vs. 2.4 ± 0.7 and after 120 min 2.5 ± 0.4 vs. 2.5 ± 0.6 nmol O2 × mg × w.w(-1) × min(-1). Respiratory control ratios were good in all experiments (8.8-11.2), ensuring functioning mitochondria.

Conclusions: These findings indicate that muscle mitochondria are not directly influenced by a factor in plasma of septic patients. The effects seen in mitochondrial function in sepsis may rather be a result of intracellular processes and signaling, such as e.g., production of reactive oxygen species.

Keywords: Mitochondria; Multiple organ failure; Rat muscle; Respiratory function; Sepsis; Septic plasma.

Figures

Fig. 1
Fig. 1
State 3 respiration of isolated rat muscle mitochondria after incubation with plasma. Isolated mitochondria were incubated with either plasma from ICU patients with severe sepsis or postoperative age-matched controls for 30 min. The respiratory rates are expressed per unit of citrate synthase (CS) activity. Red dotted lines indicate average values
Fig. 2
Fig. 2
State 3 respiration of permeabilized muscle fibers after incubation with plasma. Fibers were incubated with plasma from ICU patients with severe sepsis or healthy age-matched controls for 30 (circles) and 120 min (squares). The respiratory rates are expressed per wet weight of the incubated fibers. Each color represents a separate patient and its matched control, and black dotted line indicates average values

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